Research Article

Interactions between Human Liver Fatty Acid Binding Protein and Peroxisome Proliferator Activated Receptor Selective Drugs

Table 1

Drug binding affinity constants for human L-FABP and PPAR LBDs determined by fluorometric displacement assays.

LigandhL-FABPPPARαLBDPPARγLBDPPARδLBD

Fluorescent binding cavity probes

938401.tab.001a  
1-Anilino-8-naphthalenesulfonic acid
*logP = 6.14    = 3.55
6.0 ± 2.6 μM ntntnt
938401.tab.001b  
cis-Parinaric acid (C18:4)
*logP = 6.14    = 3.55
Kd1
0.08 ± 0.006 μM
Kd2
1.6 ± 0.3 μM
0.15 ± 0.02 μM0.4 ± 0.06 μM0.98 ± 0.12 μM

Fatty acid

938401.tab.001c  
Oleate (C18:1)
*logP = 7.7    = 5.1
Kd1
0.15 ± 0.04 μM
Kd2
2.3 ± 0.7 μM
0.21 ± 0.08 μM0.6 ± 0.015 μM1.1 ± 0.26 μM

PPARα  
selective agonist

938401.tab.001d  
GW7647
  = 5.21
0.32 ± 0.13 μM
#0.55 ± 0.17 μM
0.035 ± 0.006 μM6.8 ± 1.3 μM34 ± 6.6 μM
938401.tab.001e  
GW590735
*logP = 5.22    = 1.61
20 ± 3.8 μM0.06 ± 0.004 μM4.4 ± 2.3 μM23 ± 4.0 μM
938401.tab.001f  
Fenofibric acid  
logP = 3.86    = −0.04
1.0 ± 0.2 μM10 ± 3.0 μM79 ± 2.5 μM49 ± 4.0 μM

PPARγ  
selective agonist

938401.tab.001g  
GW1929
logP = 5.73    = 2.63
1.6 ± 0.7 μM4.8 ± 1.1 μM0.10 ± 0.03 μMnd
938401.tab.001h  
Troglitazone
logP = 5.18     = 6.23
1.7 ± 0.5 μMnd0.46 ± 0.1 μMnd
938401.tab.001i  
Rosiglitazone
logP = 2.56    = 1.47
2.8 ± 1.1 μMnd0.09 ± 0.02 μMnd

PPARδ  
selective agonist

938401.tab.001j  
L-165,041
logP = 4.98    = 1.37
1.4 ± 0.6 μM
#2.3 ± 0.5 μM
4.2 ± 0.4 μM12 ± 2.1 μM0.8 ± 0.3 μM

nd: no binding detected. An accurate measure of the could not be determined due to the combination of a low binding affinity of the receptor and the poor solubility of the drug.
nt: not tested.
*The logP and values for the compounds were calculated using the ACD Labs software.
Determined by cis-parinaric acid displacement assay with L-FABP.